PROJECT SUMMARY: The purpose of this Mentored Research Scientist Development Award is to prepare the candidate for a successful long-term career in medical rehabilitative research. The candidate will receive primary sponsorship from a senior-level scientist who will provide the candidate with a period of intensive, focused training in the areas of motor cortical neurophysiology, motor cortical plasticity following stroke, and the use of transcranial magnetic stimulation as a research tool to measure cortical excitability. The purpose of the research proposed here is to determine mechanisms of bilateral leg control in individuals with post- stroke hemiparesis; specifically, to determine the effects of the sensorimotor state of one leg on the motor behavior of the opposite leg. Three studies will be undertaken to determine: 1) does damage to the motor cortex cause specific deficits in bilateral more than unilateral cyclical ankle movements? 2) to what extent do ipsilateral uncrossed corticospinal pathways contribute to unilateral and bilateral cyclical ankle movements in individuals with motor cortical stroke? and 3) does damage to the motor cortex impair bilateral leg motor responses to a novel unilateral perturbation during walking? To answer these questions, 3-D movement kinematics and electromyography will be recorded from subjects with hemiparesis caused by motor cortical stroke and healthy age- and gender-matched control subjects performing ankle movement tasks and walking. Results will help explain the specific function of the motor cortex and corticospinal pathway and will provide a basis for the development of novel rehabilitation techniques to recover normal locomotor function in individuals with post-stroke hemiparesis. The mentorship provided in this plan will help direct the candidate toward independence as an investigator and lend significant progress toward the candidate's long- term research goal of understanding interlimb coordination during human locomotion and mechanisms for recovery of locomotor function following neurological damage. RELEVANCE: This research will have broad impact on public health, as stroke is a leading cause of long- term disability and leaves many of its victims unable to walk without assistance (AHA 2005). Findings from these studies are expected to help lead to the development of new treatments aimed at stroke rehabilitation generally and gait recovery specifically.